Abstract：
:Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) by precise regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling. The hESC-derived TEPs further mature into functional TECs that support T cell development upon transplantation into thymus-deficient mice. Importantly, the engrafted TEPs produce T cells capable of in vitro proliferation as well as in vivo immune responses. Thus, hESC-derived TEP grafts may have broad applications for enhancing engraftment in cell-based therapies as well as restoring age- and stress-related thymic decline.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Parent AV,Russ HA,Khan IS,LaFlam TN,Metzger TC,Anderson MS,Hebrok Mdoi
10.1016/j.stem.2013.04.004subject
Has Abstractpub_date
2013-08-01 00:00:00pages
219-29issue
2eissn
1934-5909issn
1875-9777pii
S1934-5909(13)00140-9journal_volume
13pub_type
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